title: Identification of meningococcal genes necessary for colonization of human upper airway tissue.
abstract: Neisseria meningitidis is an exclusively human pathogen that has evolved primarily to colonize the nasopharynx rather than to cause systemic disease. Colonization is the most frequent outcome following meningococcal infection and a prerequisite for invasive disease. The mechanism of colonization involves attachment of the organism to epithelial cells via bacterial type IV pili (Tfp), but subsequent events during colonization remain largely unknown. We analyzed 576 N. meningitidis mutants for their capacity to colonize human nasopharyngeal tissue in an organ culture model to identify bacterial genes required for colonization. Eight colonization-defective mutants were isolated. Two mutants were unable to express Tfp and were defective for adhesion to epithelial cells, which is likely to be the basis of their attenuation in nasopharyngeal tissue. Three other mutants are predicted to have lost previously uncharacterized surface molecules, while the remaining mutants have transposon insertions in genes of unknown function. We have identified novel meningococcal colonization factors, and this should provide insights into the survival of this important pathogen in its natural habitat.
authors.affiliation: Centre for Molecular Microbiology and Infection, Department of Microbiology, Flowers Building, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Exley
authors.forename: Richard
authors.initials: R
authors.lastname: Sim
authors.forename: Linda
authors.initials: L
authors.lastname: Goodwin
authors.forename: Megan
authors.initials: M
authors.lastname: Winterbotham
authors.forename: Muriel C
authors.initials: MC
authors.lastname: Schneider
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Tang
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000502:physiology*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000382:microbiology; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016254:Mutagenesis, Insertional; D009305:Nasopharynx / Q000382:microbiology*; D009345:Neisseria meningitidis / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D009924:Organ Culture Techniques; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D037521:Virulence Factors